This renewal application requests continued funding of a predoctoral training program in cellular and molecular biology at Yale University. Since its inception in 1975, the goal of the program has been to provide trainees with both a strong intellectual foundation through coursework and rigorous experimental training in research areas that take molecular and mechanistic approaches to a broad range of basic biological problems. Students and faculty participating in this training program are from several departments, including the main undergraduate campus and the School of Medicine. Thus, the training program fosters connections that transcend departmental boundaries. Much of the research carried out by our students has clear relevance to human health and disease. Students supported by the training program will be in their first, second, or third year of graduate school. The students arrive at Yale as members of the campus-wide Combined Program in the Biological and Biomedical Sciences (BBS). They come with a range of backgrounds in biology, biochemistry, chemistry, genetics, molecular biology and physics, and all students have had significant research experience before graduate school. In their first year, students will take courses that provide general knowledge in disciplines related to cellular and molecular biology and a conceptual grounding for critical evaluation of research design and methods. Students will also carry out research rotations in at least three laboratories selected according to their research interests. By the end of the first year, students will choose their thesis research advisor and affiliate with an appropriate academic department. During the second year, academic requirements for candidacy in the Ph.D. degree will be completed, including a qualifying exam in which the student prepares and defends a thesis proposal. By the third year, a thesis advisory committee will be assembled to guide each student to the completion of his or her Ph.D. training. Teaching experience is an essential part of training, and all students teach with supervision and guidance from the faculty. The average time to graduation is six years.